The research is a continuation of that which was begun in 1960 under Grant GM 07256. The goal is to gain further knowledge of the relationships between the chemical structures and the biological functions of proteins. Bovine pancreatic ribonuclease and deoxyribonuclease, the structures of both of which have now been determined in this study, will be examined in greater depth. Selective methods of cleavage will be sought for removing nonessential sections of the polypeptide chains in order to define more precisely the parts of the molecules most directly concerned in catalysis. Selective proteolysis is also being applied to study of the orientation of rhodopsin in the lipid bilayer of the rod outer segments from bovine eyes. Derivatzation, including the addition of carbohydrate side chains, is being applied to ribonuclease to study the effect of a change in the surface of the enzyme on its biological properties. Derivatization of beef liver arginase by p-guanidinophenacyl bromide is being used to label the active center of that enzyme. Research under NS 09639 is providing information on phosphodiesterases in brain that may be candidates for structural study under this grant. The facilities of this laboratory support in part the independent researches being conducted by James M. Manning under AM 16224 on the modification of hemoglobin S by cyanate. The significance of expeditious determinations of protein structures is the provision of basic information from which enzymatic and structural abnormalities can be understood in molecular terms.